Artificial Processive Catalytic Systems.

Processive catalysts remain attached to a substrate and perform multiple rounds of catalysis. They are abundant in nature. This review highlights artificial processive catalytic systems, which can be divided into (A) catalytic rings that move along a polymer chain, (B) catalytic pores that hold polymer chains and decompose them, (C) catalysts that remain attached to and move around a cyclic substrate via supramolecular interactions, and (D) anchored catalysts that remain in contact with a substrate via multiple catalytic interactions (see frontispiece).

The average magnetic anisotropy of polystyrene in polymersomes self-assembled from poly(ethylene glycol)-b-polystyrene.

Using the diamagnetic anisotropy of polymers for the characterization of polymers and polymer aggregates is a relatively new approach in the field of soft-matter and polymer research. So far, a good and thorough quantitative description of these diamagnetic properties has been lacking. Using a simple equation that links the magnetic properties of an average polymer repeating unit to those of the polymer vesicle of any shape, we measured, using magnetic birefringence, the average diamagnetic anisotropy of a polystyrene (PS) repeating unit, ΔχPS, inside a poly(ethylene glycol)-polystyrene (PEG-PS) polymersome membrane as a function of the PS-length and as a function of the preparation method. All obtained values of ΔχPS have a negative sign which results in polymers tending to align perpendicular to an applied magnetic field. Combined, the same order of magnitude of ΔχPS (10-12 m3 mol-1) for all polymersome shapes proves that the individual polymers are organized similarly regardless of the PS length and polymersome shape. Furthermore, the value found is only a fraction (∼1%) of what it can maximally be due to the random coiling of the polymers. We, therefore, predict that further ordering of the polymers within the membrane could lead to similar responses at much lower magnetic fields, possibly obtainable with permanent magnets, which would be highly advantageous for practical applications.

Kinetic enantio-recognition of chiral viologen guests by planar-chiral porphyrin cages.

The kinetic enantio-recognition of chiral viologen guests by planar-chiral porphyrin cage compounds, measured in terms of ΔΔG‡on, is determined by the planar-chirality of the host and influenced by the size, as measured by ion mobility-mass spectrometry, but not the chirality of its substituents.

Enantiodivergent Sulfoxidation Catalyzed by a Photoswitchable Iron Salen Phosphate Complex.

Here we describe a photoswitchable iron(III) salen phosphate catalyst, which is able to catalyze the enantiodivergent oxidation of prochiral aryl alkyl sulfides to chiral aryl alkyl sulfoxides. The stable (S)-axial isomer of the catalyst produced enantioenriched sulfoxides with the (R)-configuration in up to 75 % e.e., whereas the photoisomerized metastable (R)-axial isomer of the catalyst favored the formation of (S)-sulfoxides in up to 43 % e.e. The maximum Δe.e. value obtained in the enantiodivergent sulfoxidation was 118 %, which is identical to the maximum Δe.e. value that was measured in the enantiodivergent epoxidation of alkenes by a related recently described Mn1 catalyst. This iron-based catalyst broadens the scope of photoswitchable enantiodivergent catalysts and may be used in the future to develop a photoswitchable catalytic system that can write digital information on a polymer chain in the form chiral sulfoxide functions.

Enantiodivergent epoxidation of alkenes with a photoswitchable phosphate manganese-salen complex.

The development of enantiodivergent catalysts capable of preparing both enantiomeric products from one substrate in a controlled fashion is challenging. Introducing a switching function into the catalyst can address this challenge, allowing the chiral reaction environment to reversibly change during catalysis. Here we report a photoswitchable phosphate ligand, derived from 2,2'-biphenol, which axially coordinates as the counter ion to an achiral manganese(III) salen catalyst, providing the latter with the ability to switch stereoselectivity in the epoxidation of alkenes. The enantiomers of the chiral ligand exist as a pair of pseudo-enantiomers, which can be interconverted by irradiation with light of different wavelengths. The opposite axial chirality of these pseudo-enantiomers is efficiently transferred to the manganese(III) salen catalyst. With this switchable supramolecular catalyst, the enantioselectivity of the epoxidation of a variety of alkenes can be controlled, resulting in opposite enantiomeric excesses of the epoxide products. This transfer of chirality from a photoswitchable anionic ligand to a metal complex broadens the scope of supramolecular catalysts.

Mechanistic Studies on the Epoxidation of Alkenes by Macrocyclic Manganese Porphyrin Catalysts.

Macrocyclic metal porphyrin complexes can act as shape-selective catalysts mimicking the action of enzymes. To achieve enzyme-like reactivity, a mechanistic understanding of the reaction at the molecular level is needed. We report a mechanistic study of alkene epoxidation by the oxidant iodosylbenzene, mediated by an achiral and a chiral manganese(V)oxo porphyrin cage complex. Both complexes convert a great variety of alkenes into epoxides in yields varying between 20-88 %. We monitored the process of the formation of the manganese(V)oxo complexes by oxygen transfer from iodosylbenzene to manganese(III) complexes and their reactivity by ion mobility mass spectrometry. The results show that in the case of the achiral cage complex the initial iodosylbenzene adduct is formed on the inside of the cage and in the case of the chiral one on the outside of the cage. Its decomposition leads to a manganese complex with the oxo ligand on either the inside or outside of the cage. These experimental results are confirmed by DFT calculations. The oxo ligand on the outside of the cage reacts faster with a substrate molecule than the oxo ligand on the inside. The results indicate how the catalytic activity of the macrocyclic porphyrin complex can be tuned and explain why the chiral porphyrin complex does not catalyze the enantioselective epoxidation of alkenes.

113Cd as a Probe in NMR Studies of Allosteric Host-Guest-Ligand Complexes of Porphyrin Cage Compounds.

Cadmium porphyrin cage compounds Cd1 and 113 Cd1 have been synthesized from the free base porphyrin cage derivative H21 and Cd(OAc)2 ⋅ 2 H2O or 113Cd(OAc)2 ⋅ 2 H2O, respectively. The compounds form allosteric complexes with the positively charged guests N,N'-dimethylimidazolium hexafluorophosphate (DMI) and N,N'-dimethylviologen dihexafluorophosphate (Me2V), which bind in the cavity of the cage, and tbupy, which coordinates as an axial ligand to the outside of the cage. In the presence of tbupy, the binding of DMI in Cd1 is enhanced by a factor of ∼31, while the presence of DMI or Me2V in the cavity of Cd1 enhances the binding of tbupy by factors of 55 and 85, respectively. The X-ray structures of the coordination complexes of Cd1 with acetone, acetonitrile, and pyridine, the host-guest complex of Cd1 with a bound viologen guest, and the ternary allosteric complex of Cd1 with a bound DMI guest and a coordinated tbupy ligand, were solved. These structures revealed relocations of the cadmium center in and out of the porphyrin plane, depending on whether a guest or a ligand is present. 113Cd NMR could be employed as a tool to quantify the binding of guests and ligands to 113 Cd1. 1D EXSY experiments on the ternary allosteric system Cd1-tbupy-Me2V revealed that the coordination of tbupy significantly slowed down the dissociation of the Me2V guest. Eyring plots of the dissociation process revealed that this kinetic allosteric effect is entropic in nature.

Paramagnetic relaxation enhancement NMR as a tool to probe guest binding and exchange in metallohosts.

Paramagnetic metallohost systems can bind guest molecules and find application as biomimetic catalysts. Due to the presence of the paramagnetic metal center, rigorous characterization of these systems by NMR spectroscopy can be very difficult. We report here that metallohost-guest systems can be studied by using the paramagnetic relaxation enhancement (PRE) effect. Manganese(III) porphyrin cage compounds are shown through their PRE to thread and bind viologen guests, including a polymeric one. The binding constants and dethreading activation parameters are lower than those of the metal-free porphyrin cage compounds, which is proposed to be a result of charge repulsion of the trivalent metal center and dicationic viologen guest. The threading rate of the manganese(III) porphyrin cage onto the polymer is more than 10 times faster than that of the non-metallated one, which is ascribed to initial binding of the cage to the polymer chain prior to threading, and to an entron effect.

Enantioselective synthesis of chiral porphyrin macrocyclic hosts and kinetic enantiorecognition of viologen guests.

The construction of macromolecular hosts that are able to thread chiral guests in a stereoselective fashion is a big challenge. We herein describe the asymmetric synthesis of two enantiomeric C 2-symmetric porphyrin macrocyclic hosts that thread and bind different viologen guests. Time-resolved fluorescence studies show that these hosts display a factor 3 kinetic preference (ΔΔG ‡ on = 3 kJ mol-1) for threading onto the different enantiomers of a viologen guest appended with bulky chiral 1-phenylethoxy termini. A smaller kinetic selectivity (ΔΔG ‡ on = 1 kJ mol-1) is observed for viologens equipped with small chiral sec-butoxy termini. Kinetic selectivity is absent when the C 2-symmetric hosts are threaded onto chiral viologens appended with chiral tails in which the chiral moieties are located in the centers of the chains, rather than at the chain termini. The reason is that the termini of the latter guests, which engage in the initial stages of the threading process (entron effect), cannot discriminate because they are achiral, in contrast to the chiral termini of the former guests. Finally, our experiments show that the threading and de-threading rates are balanced in such a way that the observed binding constants are highly similar for all the investigated host-guest complexes, i.e. there is no thermodynamic selectivity.

Allosteric Guest Binding in Chiral Zirconium(IV) Double Decker Porphyrin Cages.

Chiral zirconium(IV) double cage sandwich complex Zr(1)2 has been synthesized in one step from porphyrin cage H21. Zr(1)2 was obtained as a racemate, which was resolved by HPLC and the enantiomers were isolated in >99.5 % ee. Their absolute configurations were assigned on the basis of X-ray crystallography and circular dichroism spectroscopy. Vibrational circular dichroism (VCD) experiments on the enantiomers of Zr(1)2 revealed that the chirality around the zirconium center is propagated throughout the whole cage structure. The axial conformational chirality of the double cage complex displayed a VCD fingerprint similar to the one observed previously for a related chiral cage compound with planar and point chirality. Zr(1)2 shows fluorescence, which is quenched when viologen guests bind in its cavities. The binding of viologen and dihydroxybenzene derivatives in the two cavities of Zr(1)2 occurs with negative allostery, the cooperativity factors α (=4 K2/K1) being as low as 0.0076 for the binding of N,N'-dimethylviologen. These allosteric effects are attributed to a pinching of the second cavity as a result of guest binding in the first cavity.

Engineered protein cages for selective heparin encapsulation.

A heparin-specific binding peptide was conjugated to a cowpea chlorotic mottle virus (CCMV) capsid protein, which was subsequently allowed to encapsulate heparin and form capsid-like protein cages. The encapsulation is specific and the capsid-heparin assemblies display negligible hemolytic activity, indicating proper blood compatibility and promising possibilities for heparin antidote applications.

Host-Guest Exchange of Viologen Guests in Porphyrin Cage Compounds as Studied by Selective Exchange Spectroscopy (1D EXSY) NMR.

Dynamics in complexes of porphyrin cage compounds and viologen-derived guest molecules are investigated by selective exchange NMR spectroscopy (1D EXSY). Exchange rates were found to be independent of excess guest concentration, revealing a dissociative exchange mechanism, which is accompanied by negative activation entropies, indicating significant reorganization of the host-guest complex during dissociation. Nonsymmetric viologen guests with bulky head groups had more unidirectional binding and slower exchange rates than guests with less-bulky head groups. Thermodynamic and kinetic studies revealed that the exchange process is primarily driven by the thermodynamics of binding and that guest binding can be influenced by introducing steric and electronic groups on the host . Exchange studies with guests bearing a polymer chain revealed that both slippage and full dissociation takes place and the rate constants for both processes were determined. The slippage rate constant revealed that for smaller guests exchange takes place nearly exclusively under thermodynamic control.

Double Porphyrin Cage Compounds.

The synthesis and characterization of double porphyrin cage compounds are described. They consist of two porphyrins that are each attached to a diphenylglycoluril-based clip molecule via four ethyleneoxy spacers, and are linked together by a single alkyl chain using "click"-chemistry. Following a newly developed multistep synthesis procedure we report three of these double porphyrin cages, linked by spacers of different lengths, i.e. 3, 5, and 11 carbon atoms. The structures of the double porphyrin cages were fully characterized by NMR, which revealed that they consist of mixtures of two diastereoisomers. Their zinc derivatives are capable of forming sandwich-like complexes with the ditopic ligand 1,4-diazabicyclo[2,2,2]octane (dabco).

Molecular motor-functionalized porphyrin macrocycles.

Molecular motors and switches change conformation under the influence of an external stimulus, e.g. light. They can be incorporated into functional systems, allowing the construction of adaptive materials and switchable catalysts. Here, we present two molecular motor-functionalized porphyrin macrocycles for future photo-switchable catalysis. They display helical, planar and point chirality, and are diastereomers, which differ in the relative orientation of the motor and macrocyclic components. Fluorescence, UV-vis, and 1H NMR experiments reveal that the motor-functionalized macrocycles can bind and thread different variants of viologen guests, including a one-side blocked polymeric one of 30 repeat units. The latter feature indicates that the motor systems can find the open end of a polymer chain, thread on it, and move along the chain to eventually bind at the viologen trap, opening possibilities for catalytic writing on single polymer chains via chemical routes.

Absolute configuration and host-guest binding of chiral porphyrin-cages by a combined chiroptical and theoretical approach.

Porphyrin cage-compounds are used as biomimetic models and substrate-selective catalysts in supramolecular chemistry. In this work we present the resolution of planar-chiral porphyrin cages and the determination of their absolute configuration by vibrational circular dichroism in combination with density functional theory calculations. The chiral porphyrin-cages form complexes with achiral and chiral viologen-guests and upon binding one of the axial enantiomorphs of the guest is bound selectively, as is indicated by induced-electronic-dichroism-spectra in combination with calculations. This host-guest binding also leads to unusual enhanced vibrational circular dichroism, which is the result of a combination of phenomena, such as rigidification of the host and guest structures, charge transfer, and coupling of specific vibration modes of the host and guest. The results offer insights in how the porphyrin cage-compounds may be used to construct a future molecular Turing machine that can write chiral information onto polymer chains.

Nonequilibrium Reshaping of Polymersomes via Polymer Addition.

Polymersomes are a class of artificial liposomes, assembled from amphiphilic synthetic block copolymers, holding great promise toward applications in nanomedicine. The diversity in polymersome morphological shapes and, in particular, the precise control of these shapes, which is an important aspect in drug delivery studies, remains a great challenge. This is due to a lack of general methodologies that can be applied and the inability to capture the morphologies at the nanometer scale. Here, we present a methodology that can accurately control the shape of polymersomes via the addition of polyethylene glycol (PEG) under nonequilibrium conditions. Various shapes including spheres, ellipsoids, tubes, discs, stomatocytes, nests, stomatocyte-in-stomatocytes, disc-in-discs, and large compound vesicles (LCVs) can be uniformly captured by adjusting the water content and the PEG concentration. Moreover, these shapes undergo nonequilibrium changes in time, which is reflected in their phase diagram changes. This research provides a universal tool to fabricate all shapes of polymersomes by controlling three variables: water content, PEG concentration, and time. The use of the biofriendly polymer PEG enables the application of this methodology in the field of nanomedicine.

Porphyrin cage compounds based on glycoluril - from enzyme mimics to functional molecular machines.

The study of artificial receptor molecules with the intention to mimic enzyme-substrate binding processes and catalysis in nature has always been a traditional area of research in supramolecular chemistry. Along this line, our group has developed a family of porphyrin cage compounds based on glycoluril and employed these in host-guest binding studies, as components of allosterically controlled self-assembled processes, in which structural changes in the cage upon complexation of a guest or a ligand change binding equilibria, and as enzyme mimics in supramolecular catalysis. In a recently started research program aimed at developing a new molecular approach to long-term data storage, porphyrin cage compounds are studied as molecular machines to encode information into synthetic polymer chains. In this Feature Article we will give an overview of the above aspects of our porphyrin cage compounds and place them in the context of related systems reported in the literature.

Effect of Chirality on the Binding of Viologen Guests in Porphyrin Macrocycles.

As part of a project aimed at the development of chiral processive catalysts that can write information on a polymer chain we describe the synthesis of two optically active porphyrin macrocycles, which are prepared in 3 steps from an achiral precursor compound. Fluorescence and 1H-NMR studies show that one of the macrocycles displays selectivity in the binding of chiral viologen guest molecules.

Motion Control of Polymeric Nanomotors Based on Host-Guest Interactions.

Controlling the motion of artificial self-propelled micro- and nanomotors independent of the fuel concentration is still a great challenge. Here we describe the first report of speed manipulation of supramolecular nanomotors via blue light-responsive valves, which can regulate the access of hydrogen peroxide fuel into the motors. Light-sensitive polymeric nanomotors are built up via the self-assembly of functional block copolymers, followed by bowl-shaped stomatocyte formation and incorporation of platinum nanoparticles. Subsequent addition of ß-cyclodextrin (ß-CD) leads to the formation of inclusion complexes with the trans-isomers of the azobenzene derivatives grafted from the surfaces of the stomatocytes. ß-CDs attachment decreases the diffusion rate of hydrogen peroxide into the cavities of the motors because of partly blocking of the openings of the stomatocyte. This results in a lowering of the speed of the nanomotors. Upon blue light irradiation, the trans-azobenzene moieties isomerize to the cis-form, which lead to the detachment of the ß-CDs due to their inability to form complexes with the cis-isomer. As a result, the speed of the nanomotors increases accordingly. Such a conformational change provides us with the unique possibility to control the speed of the supramolecular nanomotor via light-responsive host-guest complexation. We envision that such artificial responsive nano-systems with controlled motion could have potential applications in drug delivery.

Directional threading of a chiral porphyrin cage compound onto viologen guests.

We report the face-selective threading of a chiral porphyrin cage compound onto viologen guests that are provided on both ends with substituents of different sizes. Depending on the types of terminal groups on the guest the cage compound orients itself in one of two possible directions.